BXSB.129P2(Cg)-Tcra^tm1Mjo/TheoJ

Stock number: 007848
Research areas: Cancer Research, Cell Biology Research, Hematological Research, Immunology, Inflammation and Autoimmunity Research, Mouse/Human Gene Homologs, Research Tools

Description

BXSB-Tcrα^-/- homozygotes lack αβ⁺ T cells and do not develop the spontaneous lupus symptoms normally associated with the BXSB recombinant inbred genetic background. These BXSB-Tcrα^-/- mice may be useful for adoptive transfer experiments for studying the role of T cells in systemic autoimmunity and lupus.

Detailed description

Male mice on the BXSB recombinant inbred genetic background (see Stock No. 000740) develop spontaneous autoimmune disease closely resembling the human disease systemic lupus erythematosus (SLE), including moderate lymph node and spleen enlargement, hemolytic anemia, hypergammaglobulinemia, and immune complex glomerulonephritis. This autoimmune phenotype is associated with at least six non-MHC loci (the Y chromosome linked Yaa, Bxs1-4 on chromosome 1 and Bxs6 on chromosome 13) and defined by increased homeostatic proliferation of self-reactive T cells. Because these BXSB-Tcrα^-/- mice are homozygous for the Tcrα targeted mutation, they lack αβ⁺ T cells and do not develop spontaneous lupus symptoms. These BXSB-Tcrα^-/- mice may be useful for adoptive transfer experiments for studying the role of T cells in systemic autoimmunity and lupus.

Development

A targeting vector (isolated from a genomic library of embryonic BALB/c DNA) was designed to disrupt the Tcrα-C element C1 constant region of the gene with a neomycin cassette. This construct was electroporated into 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric founders were bred to BALB/c to generate mutant mice. These mice were then crossed with C57BL/6 inbred mice in the laboratory of Dr. Michael J. Owen (Imperial Cancer Research Fund). Mice were then sent to Dr. Argyrios N. Theofilopoulos (The Scripps Research Institute) and subsequently backcrossed to their stocks of the BXSB recombinant inbred strain (BXSB/MpScr) for at least 6 generations prior to arrival at The Jackson Laboratory. Upon arrival, mutant mice were bred with the BXSB/MpJ recombinant inbred strain (Stock No. 000740) for at least one generation to establish the mutant colony.

Allele

Symbol: Tcra^tm1Mjo
Name: targeted mutation 1, Michael J Owen
MGI accession ID: MGI:2180883
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Tcra
Marker name: T cell receptor alpha chain
Chromosome: 14
Strain of origin: 129P2/OlaHsd
Molecular note: The Tcra-C element C1 was disrupted by the insertion of a neomycin selection cassette.